HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells.
We have shown that hepatocyte growth factor/scatter factor can stimulate activation and early division of adult satellite cells in culture, and that the action of hepatocyte growth factor/scatter factor is similar to the action of the unidentified satellite cell activator found in extracts of crushed muscle. We now provide new evidence that hepatocyte growth factor/scatter factor is present in uninjured adult rat skeletal muscle and that the activating factor in crushed muscle extract is hepatocyte growth factor/scatter factor. Immunoblots of crushed muscle extract demonstrate the presence of hepatocyte growth factor/scatter factor. Furthermore, crushed muscle extract stimulates the scattering of cultured MDCK cells. Immunolocalization studies with adult rat skeletal muscle show the presence of hepatocyte growth factor/scatter factor in the extracellular matrix surrounding muscle fibers; in addition, the receptor for hepatocyte growth factor/scatter factor, c-met, is localized to putative satellite cells. In muscle from mdx mice, hepatocyte growth factor/scatter factor and c-met are colocalized in activated satellite cells in regions of muscle repair. Moreover, the satellite cell-activating activity of crushed muscle extract is abolished by preincubation with anti-hepatocyte growth factor antibodies. Finally, direct injection of hepatocyte growth factor/scatter factor into uninjured tibialis anterior muscle of 12-month-old rats stimulated satellite cell activation. These experiments demonstrate that hepatocyte growth factor/scatter factor is present in muscle, can be released upon injury, and has the ability to activate quiescent satellite cells in vivo.
Tatsumi
R
R
Department of Animal Science, Hokkaido University, Sapporo, Japan.
Anderson
J E
JE
Nevoret
C J
CJ
Halevy
O
O
Allen
R E
RE
D000818:Animals; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000502:physiology; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
D017228:Hepatocyte Growth Factor